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Biomedical subjects

G Finardi

Publications and source records attributed to G Finardi.

At least 19 recordsLinked to original sources
PubMed1992

Left ventricular function after reversal of myocardial hypertrophy in systemic hypertension, and response to acute increase of afterload by cold pressor test.

Using digitized M-mode echocardiography, the left ventricular (LV) response to acute increase in blood pressure after regression of myocardial hypertrophy due to an effective antihypertensive treatment was evaluated. Fifteen hypertensive patients with basal LV hypertrophy (LV mass greater than 230 g, and normal LV diastolic diameter) and normal LV mass after 3 to 4 months of treatment with angiotensin-converting enzyme inhibitors were selected for study. Subjects performed a cold pressor test before and after therapy. LV systolic function was normal in all subjects. LV diastolic function (impaired at basal evaluation in 13 subjects) improved after therapy in all subjects, with normalization in 10. Before treatment, the cold pressor test induced significant increases in blood pressure and heart rate without changes in LV parameters. After regression of hypertrophy, the cold pressor test induced increases in hemodynamic parameters comparable to those of the basal test, and LV parameters remained unchanged. Our results indicate that regression of myocardial hypertrophy induced by angiotensin-converting enzyme inhibitors does not impair the ability of the left ventricle to face acute increases in afterload. The improvement in LV diastolic function (found at rest after reversal of hypertrophy) persists during the cold pressor test, which confirms that it is primarily due to LV mass reduction and is not simply a consequence of decrease in afterload induced by treatment.

Adult↗
PubMed1992

Perindopril versus captopril: efficacy and acceptability in an Italian multicenter trial.

The aim of this 3-month, double-blind, double-dummy, parallel group study was to compare the antihypertensive efficacy and acceptability of perindopril (4-8 mg/day) in 54 patients (30 males, 24 females, 25-68 years of age) and captopril (50-100 mg/day) in 54 patients (39 males, 15 females, 29-66 years of age) in the treatment of essential hypertension. In a subgroup of 38 patients a complete echocardiographic study was performed. The two groups had similar (ANOVA) blood pressure (BP), heart rate (HR), body mass index, and duration of hypertension. Supine and standing BP was significantly reduced by both drugs, without differences between them. Owing to poor control of BP, hydrochlorothiazide (25 mg/day) was added to 27% of patients on perindopril and to 41% of patients on captopril (p less than 0.05). Normalization of supine diastolic BP (less than or equal to 90 mm Hg) was obtained in 67% of patients on perindopril and in 47% of patients on captopril (p less than 0.01). No change in HR was detected. Only mild untoward effects were recorded. Left ventricular mass was significantly reduced by either drug, with no change in systolic function. In conclusion, perindopril and captopril, at these doses, were both well tolerated and on average reduced BP to a similar extent; however, treatment with perindopril showed that fewer patients needed the addition of a thiazide and BP became normal in a larger number of patients.

Adult↗
PubMed1992

Tumor necrosis factor alpha induces apoptosis in mammary adenocarcinoma cells by an increase in intranuclear free Ca2+ concentration and DNA fragmentation.

The incubation of human mammary adenocarcinoma cells (BT-20) with tumor necrosis factor alpha in the absence or presence of cycloheximide resulted in progressive DNA fragmentation. This was preceded by a sustained increase in intracellular free Ca2+ concentration and was not detected in cells pretreated with intracellular Ca2+ chelators, calmodulin antagonists, or activators of protein kinase C. Image analysis of fura-2-loaded BT-20 cells treated with tumor necrosis factor alpha revealed that, in many cells, the initial increase in Ca2+ level occurred in a cellular region that corresponded to the localization of the nucleus. Our findings suggest that tumor necrosis factor alpha can promote an increase in intranuclear free Ca2+ which, in turn, may stimulate Ca(2+)-dependent endonuclease activity, resulting in DNA fragmentation and apoptosis.

Adenocarcinoma↗
PubMed1992

Continuous monitoring of right ventricular volume changes using a conductance catheter in the rabbit.

To assess the reliability of conductance (G) catheter for evaluating right ventricular (RV) volume changes, a miniature (3.5F) six-electrode catheter was developed and tested in 11 New Zealand rabbit hearts. In five animals the heart was excised; in six it was left in the thorax. RV conductance was recorded while the RV was filled with blood in 0.25-ml steps at different left ventricular (LV) volumes. Linear correlation of measured conductance vs. reference volumes was computed. RV conductance was highly correlated with reference volume [correlation coefficient (r) ranging from 0.991 to 0.999]. Slope of regression lines was not significantly affected by LV volume variations in 1-ml steps or by acute conductance changes of structures surrounding the heart, whereas the intercept was affected only by the 0- to 1-ml LV volume change. In four rabbits, RV conductance changes during a cardiac cycle [stroke volume- (SV) G] were compared in vivo with electromagnetic flow probe-derived estimates of SV (SVem) as stroke volume was varied by graded inferior vena caval occlusion. SV-G correlated well with SVem (r ranging from 0.92 to 0.96). This correlation persisted after the thorax was filled with saline; however, significant differences were found in individual slopes (P < 0.001). These results show that the conductance catheter has a potential to reliably monitor in vivo relative RV volume changes in small-animal hearts.

Anesthesia↗
PubMed1992

Influence of age and sex on left ventricular anatomy and function in normals.

Using digitized M-mode echograms, we evaluated the influence of sex on age-related changes of left ventricular (LV) anatomy and function in a normal population (75 males and 75 females, subdivided in age groups for each decade from 20 to 70 years). Aging is accompanied with an increase in septal and wall thickness in both males and females and in LV diameter only in males, with a progressive increase of LV mass more pronounced in males than in females. As regards LV function we found a progressive slowing of relaxation in females and of both contraction and relaxation in males, not related to changes in LV mass.

Adult↗
PubMed1992

Impaired circadian modulation of sympathovagal activity in diabetes. A possible explanation for altered temporal onset of cardiovascular disease.

BACKGROUND: Diabetic subjects have a high incidence of cardiovascular accidents, with an altered circadian distribution. Abnormalities in the circadian rhythm of autonomic tone may be responsible for this altered temporal onset of cardiovascular disease. METHODS AND RESULTS: To assess circadian changes of sympathovagal balance in diabetes, we performed 24-hour power spectral analysis of RR interval fluctuations in 54 diabetic subjects (age, 44 +/- 2 years) with either normal autonomic function or mild to severe autonomic neuropathy and in 54 age-matched control subjects. The power in the low-frequency (LF, 0.03-0.15 Hz) and high-frequency (HF, 0.18-0.40 Hz) bands was considered an index of relative sympathetic and vagal activity, respectively. Diabetic subjects with autonomic abnormalities showed a reduction in LF compared with control subjects (5.95 +/- 0.12 In-msec2 versus 6.73 +/- 0.11, p < 0.001) and an even greater reduction in LF, particularly during the night and the first hours after awakening (5.11 +/- 0.18 In-msec2 versus 6.52 +/- 0.14, p < 0.001). Day-night rhythm in sympathovagal balance was reduced or absent in diabetic subjects compared with control subjects. CONCLUSIONS: Diabetic subjects with or without signs of autonomic neuropathy have a decreased vagal activity (and hence a relatively higher sympathetic activity) during night hours and at the same time of the day, during which a higher frequency of cardiovascular accidents has been reported. These observations may provide insight into the increased cardiac risk of diabetic patients, particularly if autonomic neuropathy is present.

Adult↗
PubMed1992

High plasma levels of catecholamines during insulin-induced hypoglycemic stress do not cause beta-adrenergic receptor sequestration.

In the present investigation insulin-induced hypoglycemia was used as a powerful stimulus to rapidly release epinephrine from the adrenal medulla. Insulin injection raised epinephrine 16-fold and doubled norepinephrine plasma levels. The aim of this attempt was to induce beta-adrenergic receptors (beta-ARs) sequestration in vivo on mononuclear leukocytes (MNLs). The number of total and surface beta-ARs was significantly increased 30 minutes after insulin administration, with only partial recovery at 90 minutes. No detectable receptor sequestration was observed: surface receptors were about 90% of total receptors in all the conditions examined. Isoproterenol-stimulated cyclic adenosine monophosphate (cAMP) accumulation was also increased after 30 minutes (+66%) and 90 minutes (+65%) of insulin injection. Basal and forskolin-stimulated intracellular cAMP values were unchanged. We conclude that, even after a strong release of catecholamines, beta-AR redistribution cannot be demonstrated on MNLs.

Adrenal Medulla↗
PubMed1992

[The evaluation of the end-ejection pressure-length relation as an index of regional contractility].

Although end-systolic pressure-length relationship (ESPLR) is now widely used as a regional substitute for the end-systolic pressure-volume relationship, there are some reservations about its use as an index of systolic performance. This study aimed at assessing whether by using end-ejection (zero aortic flow) as a definition of end-systole, ESPLR can be used to characterize myocardial performance independent of load, and if the choice of the region where to implant the sonomicrometers is critical. Ten anaesthetized dogs (16 +/- 2 kg) were instrumented with a left ventricular (LV) pressure micromanometer and an aortic flow probe. Sonomicrometers were implanted in the apical (L1) and the mid-ventricular (L2) regions of the anterior LV wall, and in the basal region of the lateral wall (L3). End-systolic pressure-length relationships were obtained during acute preload reduction induced by the inflation of a vena caval balloon. This evaluation was repeated after increasing end-diastolic pressure to 14-18 mmHg (delta PL), after increasing systolic pressure by 15 (delta P-I) and 25 mmHg (delta P-II) with graded descending aorta occlusion, and during dobutamine infusions at 2.5 (Db 2.5) and 5 micrograms/kg/min (Db5). End-systolic pressure-length relationships (r > 0.97; pressure range: 70-100 mmHg) were characterized by their slopes (Ees), the extrapolated intercept at zero pressure (L0) and the values of segment length at a pressure of 75 (L75) and 100 mmHg (L100). In all the myocardial regions studied by sonomicrometry, the increments in preload and afterload did not significantly shift ESPLR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Noninvasive assessment of the relationship between cardiac and autonomic function in diabetes.

In order to assess a possible relationship between left ventricular (LV) function and cardiac autonomic involvement in type-1 insulin dependent diabetes, we performed M-mode echocardiograms and autonomic function tests in 21 patients (mean age +/- SD, 38 +/- 11 years, range 18-55, 16 male and 5 female). In 7 patients and in 21 age-matched controls the echocardiogram was also recorded before and during handgrip. At rest, ventricular function abnormalities were found only in 4 subjects, and no significant correlation was found between echocardiographic parameters and autonomic function tests. Unlike controls, during handgrip diabetic subjects failed to increase peak Vcf and peak filling rate, and increased their left ventricular end-systolic diameter. The changes in LV parameters during handgrip were significantly correlated with resting autonomic function tests (p less than 0.025). Our results suggest that resting cardiac function may be normal in diabetics despite high incidence of abnormal autonomic tests. Latent abnormalities of left ventricular function can be unmasked by acute haemodynamic challenges such as handgrip, and are correlated with abnormalities in autonomic function tests.

Adolescent↗
PubMed1991

Time course of pressure and flow in ascending aorta during ejection.

To analyze aortic flow and pressure relationships, 10 closed-chest anaesthetised dogs were instrumented with electromagnetic aortic flow probes and micromanometers in the left ventricle and ascending aorta. Left ventricular ejection time was divided into: time to peak flow (T1) (both pressure and flow rising), peak flow to peak pressure time (T2) (pressure rising, flow decreasing), and peak pressure to dicrotic notch time (T3) (pressure and flow both decreasing). These time intervals were expressed as percent of total ejection time. Load-active interventions rose markedly T2 (from 4.2 +/- 5.5 to 19.4 +/- 3.5 after phenylephrine (p less than 0.02); from 4.2 +/- 6.5 to 21.2 +/- 5.3 after dextran (p less than 0.02)). Conversely, dobutamine reduced T2 from 4.4 +/- 5.9 to -2.5 +/- 6.5 (p less than 0.05). Thus, during load-active interventions aortic pressure increases for a longer T2 time although forward flow is decreasing, as a result of higher aortic elastic recoil during ejection. Conversely, beta 1-adrenergic stimulation significantly shortens T2. Dynamic pressure-flow relationship is thus continuously changing during ejection. T2 seems to be inversely related to the efficiency of left ventricular ejection dynamics.

Animals↗
PubMed1991

Double-blind comparison of perindopril and captopril in hypertension. Effects on left ventricular morphology and function.

Using digitized M-mode echocardiograms, we compared, in a double-blind study, the effects of 4 to 8 mg perindopril given once daily and 25 to 50 mg captopril given twice daily on the left ventricle (LV) in 20 hypertensive patients. Both treatments significantly (P less than .001) lowered blood pressure, reducing systemic vascular resistances. After 3 months both drugs induced a comparable percentage of reduction in LV mass, with an increase in the peak rate of LV relaxation and no changes in the peak rate of LV contraction. Our results demonstrate that perindopril once daily is an effective antihypertensive agent; it is also able, like captopril, to induce regression of LV hypertrophy, with improvement in diastolic performance and no deterioration in ventricular systolic function.

Adult↗
PubMed1991

[The variability of the heart rate, arterial pressure and peripheral circulation as the indices of autonomic control in essential hypertension].

In recent years the influence of autonomic nervous system on cardiac rhythm and blood pressure has been increasingly studied by analysis of cardiovascular fluctuations, particularly in diabetic and normal persons under various physiologic conditions, while still few data exist on essential hypertension. To characterize the autonomic cardiovascular control in essential hypertension we studied 22 untreated hypertensives, diagnosed within 1 year (mean age 43 +/- 2 years, mean +/- SEM) and 16 age-matched normotensives. Recordings of RR interval, breathing activity, noninvasive blood pressure (Finapres) and skin arteriolar flow (infrared photoplethysmogram) were obtained while in supine position and after sympathetic activation induced by passive transition to upright posture (tilting table). Autoregressive power spectral analysis was then carried out, and low- (0.03-0.15 Hz, LF) and high-frequency fluctuations (0.15-0.35 Hz, HF) were measured. LF and HF have been considered as markers of sympathetic and parasympathetic activity on the heart, respectively, and as markers of sympathetic and mechanic chest activity on the circulation, respectively. In supine position both cardiac and vascular variability were similar in both hypertensive and normotensive groups. After tilting however the increase in the sympathetic component of cardiac variability was blunted in hypertensives with respect to normotensives (hypertensives LFnu from 43.6 +/- 4.7 nu to 59.4 +/- 5.1 nu, p less than 0.005; normotensives LFnu from 36.9 +/- 3.3 nu to 83.4 +/- 2.6 nu, p less than 0.001), the increase in LFnu being statistically (p less than 0.001) reduced in the hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Metabolic effects of the combination of captopril and hydrochlorothiazide in hypertensive subjects.

The medium-term (16 weeks) effects of the combination of captopril and hydrochlorothiazide (HCTZ) on some metabolic indexes, particularly on plasma lipoproteins, were evaluated in 20 mild to moderate hypertensive outpatients. After a 4-week wash-out period, the subjects were given one tablet of a new commercially available fixed combination once/daily (i.e., captopril 50 mg + HCTZ 25 mg). The dose could be titrated to a maximum of one tablet twice daily according to individual blood pressure responses. Both systolic and diastolic blood pressure significantly decreased at week 4 and showed a further decrease thereafter; the rate of responders (diastolic blood pressure at or below 90 mm Hg at the end of the study) was very high (90%). The only metabolic change was a small though significant increase in HDL cholesterol (P less than .05), almost entirely due to an increase in the denser HDL3 subfraction. The atherogenic fractions, namely total cholesterol, LDL cholesterol, and apoprotein B, showed no significant changes. Plasma triglycerides underwent a transient increase at week 8 (P less than .05) but thereafter fell. Plasma glucose, creatinine, uric acid, and potassium were unchanged. The fixed combination of captopril and HCTZ seems highly effective in lowering blood pressure and seems devoid of untoward metabolic effects. Its overall impact on the coronary risk profile in hypertensive subjects seems therefore to be favorable.

Adult↗
PubMed1990

Autonomic nervous system and microcirculation in diabetes.

In order to evaluate the occurrence of sympathetic impairment of skin microvascular control in diabetes, we evaluated the spectral analysis of forearm skin laser-Doppler fluctuations in nine insulin-dependent diabetic subjects and in 21 controls of similar age. Low-frequency oscillations (around 0.1 Hz) were significantly lower in diabetics than in controls (2.333 +/- 0.340 (mean +/- SEM) units vs. 3.486 +/- 0.093 units, P less than 0.001), whereas no significant differences were found between the two groups regarding high-frequency respiration-related oscillations. These results suggest that the loss of rhythmicity in diabetic subjects is selectively related to low-frequency oscillations, mostly under sympathetic control, and is likely to be dependent on autonomic abnormality.

Adult↗
PubMed1990

Measuring left ventricular dimensions by conductance catheter in the rabbit.

A miniaturized (3.5 F), six-electrode conductance catheter was tested in 18 anaesthetized adult rabbits (weight 3.8-4.6 kg, ethylurethane 2.5 g kg-1). In eight animals, the reference stroke volume (ref-SV) was obtained by an electromagnetic flow probe, while reference end-diastolic volume (ref-LVEDV) was computed by dividing ref-SV by undamped thermal dilution ejection fraction (ref-EF) estimates. Comparisons with conductance indexes (z-SV, z-LVEDV and z-EF) were made at baseline, subsequent levels of graded haemorrhage and reinfusion state. In 10 animals intraventricular segmental conductance was compared with echocardiographic left ventricular cross-section (5 MHz short-focus probe), in the basal state and during acute left ventricular volume changes generated by inferior vena cava balloon occlusion. In each experiment, parallel conductance due to the tissues surrounding the left ventricle (Gp) was determined by infusing a 5M NaCl solution bolus into the right ventricle. Linear regression analysis showed fairly good correlations between z-SV, z-LVEDV and z-EF and reference indexes (r = 0.84, r = 0.83, and r = 0.72, respectively; P less than 0.001 in all cases). A linear regression analysis from 17 interventions (inferior vena cava balloon occlusion) showed a good correlation between left ventricular echocardiographic cross-sectional area and conductance, and higher correlation coefficients, r ranging from 0.870 to 0.986 were obtained from continuously sampled conductance and echographic measurements. Parallel conductance Gp was correlated (r = 0.807, P less than 0.01) with the intercept of the regression line of echographic vs conductance data. The determination of Gp thus improved the accuracy of the left ventricular dimension estimate. These results add further evidence for the possibility of continuous monitoring of left ventricular dimension by means of a conductance catheter, and demonstrate the feasibility of such studies on small experimental animals.

Animals↗
PubMed1990

[Factors influencing left ventricular function in arterial hypertension].

Using digitized M-mode echograms we evaluated the role of preload, afterload, inotropic state and left ventricular (LV) mass on LV systolic and diastolic function in 2 groups of hypertensive patients: Group 1: 25 subjects (18 men, mean age 48 +/- 6 years) with normal LV mass (less than 230 g); Group 2: 25 subjects (20 men, mean age 50 +/- 8 years) with LV hypertrophy (wall hypertrophy with normal LV diameter). As control group, we evaluated 50 normal subjects, matched for age, sex and body surface area with hypertensives. LV mass was significantly (p less than 0.001) higher as respect to normals also in hypertensives with normal LV mass; indexes of LV systolic and diastolic function were similar in normals and in hypertensives with normal LV mass and significantly lower in subjects with LV hypertrophy. The end-systolic wall stress was not significantly different in the 2 groups of hypertensives. We evaluated the relative role of preload (end-diastolic LV diameter), afterload (end-systolic wall stress) inotropic state (systolic arterial pressure/end-systolic LV diameter) and LV mass on LV systolic and diastolic function using multiple regression analysis. As regards LV systolic function, the major determinant was the systolic pressure/end-systolic diameter ratio in normals, the end-systolic stress in hypertensives. As regards LV diastolic function, the major determinant was end-systolic stress in normals and hypertensives with normal LV mass, LV mass in hypertensives with myocardial hypertrophy. Preload seems not to influence LV function in normals and in hypertensives with normal LV diastolic diameter. The major determinant of LV systolic function is the inotropic state in normals and the afterload in hypertensives.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

On the role of mitochondria in cell injury caused by vanadate-induced Ca2+ overload.

Incubation of isolated rat hepatocytes with vanadate (0.25, 0.5 and 1 mM) resulted in progressive accumulation of Ca2+ in the intracellular compartments. Vanadate- induced Ca2+ accumulation was related to inhibition of the plasma membrane Ca2+-extruding system, but did not involve either enhanced plasma membrane permeability to Ca2+ or the enhanced operation of a putative Na+/Ca2+ exchanger. After an initial rise in the cytosolic free Ca2+ concentration, as revealed by phosphorylase activation, Ca2+ was sequestered predominantly by the mitochondria with little contribution from the endoplasmic reticulum. As the amount of Ca2+ in the mitochondria increased, a progressive decrease in mitochondrial membrane potential occurred, together with an impairment of the ability of these organelles to further sequester Ca2+. Associated with this, there was a decrease in intracellular ATP level, formation of surface blebs and cytotoxicity. Addition of an uncoupler to vanadate-treated hepatocytes dramatically accelerated the appearance of plasma membrane blebs and toxicity. Our results demonstrate that under conditions in which the plasma membrane Ca2+ pump is inhibited, mitochondria play an important role in protecting hepatocytes against damage induced by Ca2+ overload.

Adenosine Triphosphate↗